1. Field of the Invention
Lyme disease was first described in the late 1970's as a unique grouping of arthritic symptoms in patients from Lyme, Conn. Subsequent investigation demonstrated that the disease is caused by infection with Borrelia burgdorferi, a spirochete, following exposure to deer (ixodid) ticks. It is now known that lyme disease in humans is a multi-systemic disorder characterized by dematologic, rheumatologic, cardiac, and neurologic manifestations.
While several isolates of Borrelia burgdorferi from North America and Europe have been characterized at both the genetic and antigenic level, the unequivocal diagnosis of lyme disease remains problematic. Isolation and cultivation of borrelia from infected patients is difficult and not practical for routine diagnosis. Immunological and genetic detection methods have not become generally available, at least in part because the known major antigens of Borrelia burgdorferi have previously been thought to be coded on linear plasmid and have demonstrated significant antigenic variation with regard to the level of expression and molecular weight. There have also been reports of serological cross-reactivity with related human pathogens, such as B. hermsii (the causative agent of tick-born relapsing fever) and Treponema palladium (the causative agent of syphilis).
It would therefore be desirable to provide improved methods for diagnosing lyme disease and in particular for unequivocally determining the presence of Borrelia burgdorferi in patient samples. To provide such methods, it would be desirable to identify genetic and antigenic information which is widely conserved among Borrelia burgdorferi strains and which can be used in a variety of detection protocols. More specifically, it would be desirable to identify a conserved chromosomal gene which encodes a major antigenic protein, where the gene can serve as the basis for genetic screening assays and the antigen can serve as the basis for immunologic screening assays.
2. Description of the Background Art
Immunochemical analyses of Borrelia burgdorferi have revealed the presence of several immunodominant antigens that are recognized during the described stages of human infection. (Craft, et al. (1986). Clin. Invest. 78: 934-938; Grodzicki, et al. (1988) J. Infect. Dis. 157: 790-797; Nadal, et al. (1989) Pediatr. Res. 26: 377-382) One of the immunodominant antigens was reported to have a molecular weight of approximately 83 kD. No description or characterization of the gene encoding this antigen had been reported prior to the work which is the subject of the present application. The data included in the Experimental section hereinafter was reported in LeFebvre et al. (1990) J. Clin. Microbiol. 28: 1673-1675 and in Perng et al. (1991) Infect. Immun. 59: 2070-2074.